Research News

As cells age, fat content within them shifts

The images above show key structural proteins (actin and tubulin) as cells age. The top raw shows still dividing, and, the bottom raw shows senescent (cells that no longer divide) cells. Their comparison highlights the difference in shape of these cells. Image: UB

By CHARLOTTE HSU

“Our results add to evidence that lipids may actually play a much more active role in the body — in this case, in the process of replicative senescence, which is linked to cellular aging. This is a new, emerging field of study.”

Ekin Atilla-Gokcumen, assistant professor

Department of Chemistry

As cells age and stop dividing, their fat content changes, along
with the way they produce and break down fat and other molecules
classified as lipids, according to a new UB study.

“Traditionally, lipids have been thought of as structural
components: They store energy and form the membranes of
cells,” says G. Ekin Atilla-Gokcumen, assistant professor of
chemistry in the College of Arts and Sciences. “Our results
add to evidence that lipids may actually play a much more active
role in the body — in this case, in the process of
replicative senescence, which is linked to cellular aging. This is
a new, emerging field of study.”

By providing broad insights into the connection between lipids
and cellular aging, the findings open the door for additional
research that could one day support the development of lipid-based
approaches to preventing cell death or hastening it in cancerous
tumors.

The research, published on Jan. 19 in the journal Molecular
BioSystems, was led by Atilla-Gokcumen and Omer Gokcumen,
assistant professor of biological sciences in UB’s College of
Arts and Sciences. Co-authors include Darleny Y. Lizardo, a UB PhD
candidate in medicinal chemistry, and Yen-Lung ‘Onta’
Lin, a UB PhD candidate in biological sciences.

How lipids change as cells age

Lipids are a class of organic molecules that include fats, waxes
and sterols like cholesterol.

To study the role of these molecules in cellular aging, the
researchers grew human fibroblast cells in the lab over four months
— long enough that some cells stopped dividing, a process
known as replicative senescence.

When the researchers compared the lipid content of young cells
to older cells, some interesting trends emerged.

In senescent cells, 19 different triacylglycerols, a specific
type of lipid, accumulated in substantial amounts. These increases
occurred in both lung and foreskin fibroblasts, showing that such
changes are not limited to a single variety of cell.

To glean more information about the function of lipids in
cellular senescence and aging, the scientists used a technique
called transcriptomics to determine how cellular activity
associated with lipid-related genes changed as cells grew
older.

The analysis provided yet more evidence that the lipidome
— the collection of all lipids within cells — is highly
regulated during senescence. In cells that had stopped dividing,
the behavior of dozens of genes tied to lipid-related processes,
such as the synthesis, break down and transport of lipids, changed
significantly compared to that of all genes within the cells.
Certain lipid-linked genes became more actively expressed, meaning
they were used more often to create proteins, while others became
less so.

“A lot of research has been done on how proteins
contribute to cellular processes such as cellular senescence, but
the role of lipids is much less clear,” Gokcumen says.
“Work in this area has been very limited, and our study
provides a huge amount of data about the lipidome and lipid-linked
genes that other researchers can use to further understand how
lipids are involved in cellular aging.”

Lipid droplets: A defense against cellular aging?

The research did not draw direct conclusions about why levels of
the 19 triacylglycerols rose during cellular aging, but the project
did reveal clues as to why this may have happened, Atilla-Gokcumen
and Gokcumen say.

Atilla-Gokcumen and Gokcumen hypothesize that the
triacylglycerols in question may help the body cope with oxidative
stress, which occurs when dangerous molecules called reactive
oxygen species roam the body and cause damage to cells.

The study found that during cellular senescence, the
accumulation of triacylglycerols corresponded with a significant
increase in the levels of genes involved in responding to oxidative
stress.

Furthermore, the 19 triacylglycerols identified had chemical
properties that could help protect cells from damage caused by
oxidative stress. All had a remarkably similar structure, featuring
long chains of fatty acids, including at least one polyunsaturated
fatty acyl (PUFA) chain.

This matters because PUFA chains can bind with reactive species,
taking them out of circulation. And because triacylglycerols are
stored within solitary lipid droplets inside cells, PUFA
triacylglycerols may be able to carry out the important duty of
neutralizing the dangerous intruders without harming other
components of a cell.